The overall objective of the proposed work is to define the role played by abnormalities of glucose, insulin and lipoprotein metabolism in the genesis of atherosclerosis. During the next year we plan to focus on two aspects of this problem. The first will consist of studies aimed at defining the role played by abnormalities of insulin binding to its specific receptors, in the genesis of insulin resistance. The second aspect will involve efforts aimed at determining whether or not insulin resistance in man is present equally in all insulin-responsive tissues. In order to accomplish this second objective we will use radiolabeled glucose to determine the ability of insulin to inhibit hepatic glucose output as compared to promoting glucose uptake in patients with varying degrees of insulin resistance. BIBLIOGRAPHIC REFERENCES: Ginsberg, H., Kimmerling, G., Olefsky, J. M. and Reaven, G. M. Demonstration of insulin resistance in untreated adult onset diabetic subjects with fasting hyperglycemia. J. Clin. Invest. 55-454, 1975. Ginsberg, H., Olefsky, J.M. and Reaven, G.M. Evaluation of insulin resistance in patients with primary hyperparathyroidism. Proc. Soc. Exper. Biol. Med. 148:942, 1975.